K. Yamada et al., CHANGES IN EXTRACELLULAR NITRITE AND NITRATE LEVELS AFTER INHIBITION OF GLIAL METABOLISM WITH FLUOROCITRATE, Brain research, 762(1-2), 1997, pp. 72-78
The role of glial cells in nitric oxide production in the cerebellum o
f conscious rats was investigated with a glial selective metabolic inh
ibitor, fluorocitrate. The levels of nitric oxide metabolites (nitrite
plus nitrate) in the dialysate following in vivo microdialysis progre
ssively increased to more than 2-fold the basal levels during a 2-h in
fusion of fluorocitrate (1 mM), and the increase persisted for more th
an 2 h after the treatment. Pretreatment with N-G-nitro-L-arginine met
hyl ester attenuated the fluorocitrate-induced increase in nitric oxid
e metabolite levels. None of the glutamate receptor antagonists, inclu
ding D(-)-2-amino-5-phosphonopentanoic acid, 6,7-dinitroquinoxaline-2,
3-dione, and (+/-)-alpha-methyl-4-carboxyphenylglycine, inhibited the
fluorocitrate-induced increase. The L-arginine-induced increase was si
gnificantly reduced by fluorocitrate treatment, while N-methyl-D-aspar
tate, lpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, and ns-
(+/-)-1-amino-(1S,3R)-cyclopentane-dicarboxylic acid increased nitric
oxide metabolites levels in the fluorocitrate-treated rats, as much as
in control animals. These results suggest that glial cells play an im
portant role in modulating nitric oxide production in the cerebellum b
y regulating L-arginine availability.